The overall objectives of this Research Core are to develop and promote new understandings of the effects of urban air pollution on the human body. This goal will be implemented by pilot research projects, interactive research seminars, and pre/postdoctoral student training. Specific research activities in Research Core 4 fall within the first four of the general Research Core elements listed above, but within each broad element, there are individual specific aims. These include: 1) Determination of the movement of soluble and insoluble particles after deposition in the lung; 2) Determination of the molecular genetic and inflammatory environment of exposed respiratory tissues and cells; 3) Evaluation of the pathophysiologic mechanisms associated with the effects of these inhalants on pulmonary tissues and cellular responses; and 4) Interpretation of these relations in terms of health risks from human exposures; a major focus within elements 2 and 3 in the past has been a better understanding of the mechanism of hyperreactive airways and obstructive airway diseases, with special emphasis on asthma. How environmental pollutants affect the epithelium and airway smooth muscles has direct relevance to the response of asthmatics breathing in polluted air. In the inner cities such air pollution can lead to a condition known as urban asthma. This research, along with that in the first Core element, will form the scientific basis for new and increasing outreach focus involving the human exposure assessment research in Research Core 1. The Johns Hopkins Center for Childhood Asthma in the Urban Environment, headed by Dr. Eggleston, also may provide opportunity for new mechanistic understandings related to this human pathology. Risks for emphysema and lung cancer are also high in inner cities, and new projects in the Core with collaboration with Research Core 3 will begin to look at underlying mechanisms of these pathologies. Finally an increasingly important direction that will be expanded is the interaction of air pollution with viral infections. Two new faculty members (Jacoby and Imani) to the Core with immunologic expertise will lead this effort. A long range Research Core aim is to be able to investigate this spectrum of questions related to a variety of urban airborne pollutants, from the quantitative analysis of the exposure magnitude to a quantitative understanding of basic pathophysiologic responses of cells and tissues to these exposures. At the present time this global approach within the Research Core is fairly well developed for ozone, particulate matter, and viral infections, with studies spanning the spectrum from molecular genetics to human exposures. It is important to emphasize that the members of this Core are physiologists, pharmacologists, immunologists, pathologists, and pulmonary physicians who investigate basic mechanisms underlying environmental insults to the lung. As noted above, the investigators feel that this multi-disciplinary background is a major strength of this Research Core, providing the NIEHS Center with a unique perspective on environmental studies.